Silica-coated SPIO nanoparticles for photoacoustic detection of circulating cancer cells

Objectives Photoacoustic imaging is an emerging molecular imaging modality that shows promise in clinical applications. This imaging modality relies on the development of photoacoustic contrasts. Superparamagnetic iron oxide (SPIO) nanoparticles have been clinically proven safe and used as an MRI contrast agent approved by FDA. In this work we present an initial study of the development of silica-coated SPIO nanoparticles showing high photoacoustic signals for the potential detection of single circulating cancer cell in blood.

Methods 60 µL oleic acid coated SPIO (core size: 10 nm) in chloroform was mixed with 880 µL Igepal and 3.75 mL cyclohexane, and stirred for 30 min at room temperature. The mixture was then added 170 µL Milli-Q water, 50 µL tetraethyl orthosilicate (TEOS) and 60 µL NH4OH (28.0%~30.0%). The reaction mixture was stirred for 24 hours at room temperature, followed by an addition of acetone and centrifugation (4400 rpm, 30 min, T = 25 ºC) to break the microemulsion. The silica coated SPIO was washed with butanol, isopropanol, ethanol and water sequentially to remove surfactants and unreacted molecules. During the process an ultra-sonication was applied to wash away adsorbed materials from the SPIO and facilitate re-dispersion of precipitates. The silica-coated SPIO was finally dispersed in Milli-Q water.

Results Transmission Electron Microscope (TEM) results visually confirmed the silica coating on the SPIO. The SPIO core diameter is 10.00 ± 0.90 nm. The silica coating thickness is 2.63 ± 0.94 nm that results an overall diameter of 15.26 ± 1.65 nm. The photoacoustic signals were measured using a photoacoustic imaging system with an optical parametric oscillator (OPO) light source. The OPO provides a tunable nanosecond pulsed laser at 20 Hz from 680 nm to 970 nm. The samples were in small tubes in a tissue phantom. The photoacoustic signals of our sample show an absorptive broad band around 923 nm. The maximum photoacoustic signal of the silica-coated SPIO is about 10 times of the signal from the control sample of a SPIO without silica coating or Feridex at the same wavelength range.

Conclusions Our results demonstrate that the silica-coated SPIO is a promise candidate for photoacoustic imaging at the near infrared wavelength where the pulsed laser can penetrate deeper inside biological tissues. Ongoing and future work includes the surface functionalization for targeting prostate and breast cancer cells in peripheral blood in vitro and in vivo.